Saccharopolyspora erythraea
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ABSTRACT:
PROVIDER: PRJNA144545 | ENA |
REPOSITORIES: ENA
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Project description:Saccharopolyspora erythraea is used for industrial-scale production of erythromycin. To explore the physiological role of co-factors in regulation of primary and secondary metabolism of S. erythraea, we initially overexpressed the endogenous F1-ATPase in an erythromycin high-producing strain, E3. The engineered strain is named EA. The F1-ATPase expression resulted in a lower [ATP]/[ADP] ratio, which was accompanied by a dramatic increased production of a reddish pigment and a decreased erythromycin production. Transcriptional analysis revealed that the intracellular [ATP]/[ADP] ratio appeared to exert a global regulation on the metabolism of S.erythraea, and the lower [ATP]/[ADP] ratio induced physiological changes to restore the energy balance, mainly via pathways that tend to produce ATP or NADH. The results also indicated a state of redox stress in the engineered strain, which was correlated to the alteration of electron transport at the branch of the terminal oxidases.
2020-02-26 | GSE134767 | GEO
Project description:Knowledge about effects of cofactor perturbation on cellular metabolism is scarce with respect to Saccharopolyspora erythraea. The water-forming NADH oxidase (NOX) from Streptococcus pneumonia was expressed in S.erythraea E3, an important industrial strain for erythromycin production, at three different levels to investigate effects of intracellular redox status on secondary metabolism. NOX expression reduced the intracellular [NADH]/[NAD+] ratios significantly, although with a strong constitutive promoter NOX function was limited due to the shortage of oxygen. We demonstrated the negative correlation between [NADH]/[NAD+] ratios and biosynthesis of erythromycin in S.erythraea, but a positive correlation between the redox ratios and pigment production as well. We furthermore completed next-generation RNA sequencing of E3 and two NOX-expression strains. The transcription results showed that transfer processes of carbohydrates, DNA and chemical groups were altered resulting in metabolic shifts to supply more NADH for NOX fully functioning. Additionally, redox status affected transcription of several genes by allosteric effects on their transcription initiation. Specifically, transcriptional analysis along with enzymatic assay suggested that redox status influenced biosynthesis of erythromycin indirectly by allosteric effects on biosynthesis of the secondary messenger, c-di-GMP. The present work provides a basis for future cofactor manipulation in S.erythraea for further improvement of erythromycin production.
2020-08-04 | GSE144067 | GEO
Project description:Source of the antibiotic erythromycin
| PRJNA18491 | ENA
Project description:Comparative genomics reveals new molecular targets for accelerated strain improvement of rifamycin B-producing strains
| PRJNA219644 | ENA
Project description:Information about molecular mechanisms underlying improvement of antibiotic-producing microorganisms with traditional mutation and screening approach is largely missing. This information is essential to develop rational approaches to strain improvement. In this study by using comparative genomic analysis we have identified all genetic changes that have occurred during development of an erythromycin overproducer, which was obtained by the traditional mutate-and-screen method. Compared with parental Saccharopolyspora erythraea NRRL 2338, a total of 117 deletion, 78 insertion and 12 transposition sites were found across the genome of the overproducer. Among them, 71 insertion/deletion sites mapped within coding sequences (CDSs) generating frame-shift mutations. Moreover, single nucleotide variations affecting a total of 144 CDSs were identified between the two genomes. Overall, variations affect a total of 227 proteins in the genome of the overproducer. The analysis of metabolic pathways demonstrated that a considerable number of mutations affect genes coding for key enzymes involved in central carbon and nitrogen metabolism, and biosynthesis of secondary metabolites, redirecting common precursors toward erythromycin biosynthesis. Interestingly, several mutations inactivate genes coding for proteins that play fundamental roles in basic transcription and translation machineries including the transcription anti-termination factor NusB and the transcription elongation factor Efp. These mutations, along with those affecting genes coding for pleiotropic or pathway-specific regulators, may affect global expression profile. Consistent transcriptomic data were obtained from a comparative analysis between NRRL 2338 and the erythromycin overproducer gene expression profiling performed with DNA microarray. Genomic data also indicated that the mutate-and-screen process might have been accelerated by mutations in DNA repair genes. Our findings, largely unanticipated, reveal new targets suitable for rationale improvement of antibiotic-producing strains. According to a rough estimate, actinomycetes, which are among the most abundant bacteria in soil, produce over 70% of naturally occurring antibiotics and other biologically active substances including anti-tumour agents and immunosuppressants. However, these microorganisms must often be genetically improved for higher production before they can be used in the industry. Strain improvement has traditionally relied on multiple rounds of random mutagenesis and screening. This method is essentially empirical, and notably time-consuming and expansive. Currently, the availability of molecular genetics tools and useful information about the biosynthetic pathways and genetic control for most of biologically active substances has opened the way for improving strains by rational engineering. These rational strain improvement strategies benefit of the support of genomic and post-genomic technologies. In this study by using comparative genomic analysis we have identified all genetic changes that have occurred during development of an erythromycin overproducer, which was obtained by the traditional mutate-and-screen method. Our findings, largely unanticipated, reveal new molecular targets suitable for rationale improvement of antibiotic-producing strains by recombinant technologies, and support the evidence that combining classical and recombinant strain improvement with a solid fermentation development program is the best way to improve production of biologically active substances. Erythromycin over-producing Strain at various time points
2012-05-23 | E-GEOD-30600 | biostudies-arrayexpress
Project description:Phenotype and expression profile of S. erythraea rifampicin-resistant (rif) mutants affected in erythromycin production
| PRJNA113291 | ENA
Project description:Source of the antibiotic erythromycin
| PRJNA17885 | ENA
Project description:Source of the antibiotic erythromycin
| PRJEA18489 | ENA
Project description:Erythromycin is a medically important antibiotic, biosynthesized by the actinomycete Saccharopolyspora erythraea. We used transcriptomic approach to compare whole genome expression in erythromycin high-producing strain, compared to the wild type S. erythraea strain in four stages of fermentation.
2016-06-22 | GSE65007 | GEO
Project description:Information about molecular mechanisms underlying improvement of antibiotic-producing microorganisms with traditional mutation and screening approach is largely missing. This information is essential to develop rational approaches to strain improvement. In this study by using comparative genomic analysis we have identified all genetic changes that have occurred during development of an erythromycin overproducer, which was obtained by the traditional mutate-and-screen method. Compared with parental Saccharopolyspora erythraea NRRL 2338, a total of 117 deletion, 78 insertion and 12 transposition sites were found across the genome of the overproducer. Among them, 71 insertion/deletion sites mapped within coding sequences (CDSs) generating frame-shift mutations. Moreover, single nucleotide variations affecting a total of 144 CDSs were identified between the two genomes. Overall, variations affect a total of 227 proteins in the genome of the overproducer. The analysis of metabolic pathways demonstrated that a considerable number of mutations affect genes coding for key enzymes involved in central carbon and nitrogen metabolism, and biosynthesis of secondary metabolites, redirecting common precursors toward erythromycin biosynthesis. Interestingly, several mutations inactivate genes coding for proteins that play fundamental roles in basic transcription and translation machineries including the transcription anti-termination factor NusB and the transcription elongation factor Efp. These mutations, along with those affecting genes coding for pleiotropic or pathway-specific regulators, may affect global expression profile. Consistent transcriptomic data were obtained from a comparative analysis between NRRL 2338 and the erythromycin overproducer gene expression profiling performed with DNA microarray. Genomic data also indicated that the mutate-and-screen process might have been accelerated by mutations in DNA repair genes. Our findings, largely unanticipated, reveal new targets suitable for rationale improvement of antibiotic-producing strains. According to a rough estimate, actinomycetes, which are among the most abundant bacteria in soil, produce over 70% of naturally occurring antibiotics and other biologically active substances including anti-tumour agents and immunosuppressants. However, these microorganisms must often be genetically improved for higher production before they can be used in the industry. Strain improvement has traditionally relied on multiple rounds of random mutagenesis and screening. This method is essentially empirical, and notably time-consuming and expansive. Currently, the availability of molecular genetics tools and useful information about the biosynthetic pathways and genetic control for most of biologically active substances has opened the way for improving strains by rational engineering. These rational strain improvement strategies benefit of the support of genomic and post-genomic technologies. In this study by using comparative genomic analysis we have identified all genetic changes that have occurred during development of an erythromycin overproducer, which was obtained by the traditional mutate-and-screen method. Our findings, largely unanticipated, reveal new molecular targets suitable for rationale improvement of antibiotic-producing strains by recombinant technologies, and support the evidence that combining classical and recombinant strain improvement with a solid fermentation development program is the best way to improve production of biologically active substances.
2012-05-24 | GSE30600 | GEO